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Vol. 10, Issue 7, 2361-2375, July 1999



*Division of Experimental Medicine, Beth Israel Deaconess Medical
Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115;
The cytoskeleton plays an important role in neuronal morphogenesis.
We have identified and characterized a novel actin-binding protein,
termed Mayven, predominantly expressed in brain. Mayven contains a BTB
(broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger)
domain-like structure in the predicted N terminus and "kelch
repeats" in the predicted C-terminal domain. Mayven shares 63%
identity (77% similarity) with the Drosophila ring canal ("kelch") protein. Somatic cell-hybrid analysis indicated that the human Mayven gene is located on chromosome 4q21.2, whereas the
murine homolog gene is located on chromosome 8. The BTB/POZ domain of
Mayven can self-dimerize in vitro, which might be important for its
interaction with other BTB/POZ-containing proteins. Confocal microscopic studies of endogenous Mayven protein revealed a highly dynamic localization pattern of the protein. In U373-MG
astrocytoma/glioblastoma cells, Mayven colocalized with actin filaments
in stress fibers and in patchy cortical actin-rich regions of the cell
margins. In primary rat hippocampal neurons, Mayven is highly expressed in the cell body and in neurite processes. Binding assays and far
Western blotting analysis demonstrated association of Mayven with
actin. This association is mediated through the "kelch repeats" within the C terminus of Mayven. Depolarization of primary hippocampal neurons with KCl enhanced the association of Mayven with actin. This
increased association resulted in dynamic changes in Mayven distribution from uniform to punctate localization along neuronal processes. These results suggest that Mayven functions as an
actin-binding protein that may be translocated along axonal processes
and might be involved in the dynamic organization of the actin
cytoskeleton in brain cells.
BioMedical Imaging Laboratory, Harvard School of Public
Health, Boston, Massachusetts 02115; and
Section of
Medical Genetics and Molecular Medicine, Children's Mercy Hospital,
University of Missouri Kansas City School of Medicine, Kansas
City, Missouri 64108
Corresponding author.
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